GB2207766A - Methods of obtaining images representing the distribution of paramagnetic molecules in solution - Google Patents
Methods of obtaining images representing the distribution of paramagnetic molecules in solution Download PDFInfo
- Publication number
- GB2207766A GB2207766A GB08818705A GB8818705A GB2207766A GB 2207766 A GB2207766 A GB 2207766A GB 08818705 A GB08818705 A GB 08818705A GB 8818705 A GB8818705 A GB 8818705A GB 2207766 A GB2207766 A GB 2207766A
- Authority
- GB
- United Kingdom
- Prior art keywords
- nmr
- obtaining
- distribution
- epr
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 14
- 230000005298 paramagnetic effect Effects 0.000 title claims description 9
- 238000003384 imaging method Methods 0.000 claims description 9
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 claims description 6
- 230000005855 radiation Effects 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 238000004435 EPR spectroscopy Methods 0.000 description 25
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- 230000005291 magnetic effect Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000003990 capacitor Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001983 electron spin resonance imaging Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/60—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using electron paramagnetic resonance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/62—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using double resonance
Landscapes
- Physics & Mathematics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
Description
r n h- 0 '17 6 o - 1 131435 METHODS OF OBTAINING IMAGES REPRESENTING THE
DISTRIBUTION OF PARAMAGNETIC MOLECULES IN SOLUTION This invention relates to methods of obtaining images representing the distribution of paramagnetic molecules in solution, including free radicals. The invention has application inter alia in the determination of the distribution of free radicals, which may have been previously injected, in living tissue.
Electron paramagnetic resonance (EPR) imaging using methods analogous to those employed in nuclear magnetic resonance (NMR) imaging but at much higher nutation frequencies is known.
However, in view of the strong magnetic field gradients necessary to achieve good spatial resolution, EPR imaging has so far been restricted to small samples.
Where a solution contains a paramagnetic solute it is also known to excite EPR resonance of t-he solute and observe the NMR resonance of nuclei in the solvent. Under favourable conditions saturation of the EPR resonance in the solute causes a dramatic enhancement of the NMR signal from the solvent. In particular, the effect requires that the NMR nuclei be relaxed by their interactions with the unpaired electrons of the solute. 20 It is an object of the invention to utilise the above phenomenon to obtain image information of paramagnetic free radicals in solution. According to the invention a method of obtaining image information representing the distribution of paramagnetic molecules in solution comprises the steps of applying radio- frequency radiation to excite EPR resonance in the solute and obtaining an NMR image signal of selected nuclei of the solvent, the signal from those selected nuclei which interact with electrons excited by the rf radiation being enhanced.
In carrying out the invention there may also be included the additional steps of obtaining an NMR image signal of said selected nuclei which is unenhanced, and deriving image - 2 information representing the difference between the enhanced and unenhanced Image signals.
The NMR image signal may be obtained by any conventional NMR imaging technique. In prefered embodiments the said selected nuclei are protons.
The maximum possible enhancement Is given by -vS12v1 where vS and vj are. the EPR and NMR frequencies respectively; for protons, this corresponds to a factor of -330. (A negative enhancement means that the NMR signal changes phase by 180 degrees upon irradiation of the EPR resonance, while Its magnitude increases by the numerical factor). The observed enhancement factor depends on the degree of saturation of the EPR resonance of the solute and therefore on the strength of the irradiating magnetic field. It also depends on the concentration -of the paramagnetic compound, the particular solvent and solute under study, the temperature of the sample and the strength of the static magnetic field. In order that the invention may be more fully understood reference will now be made to the accompanying drawing in which: 20 Fig. 1 shows the layout of an EPR transmitter coil and an NMR receiver coil used in apparatus for carrying out the invention. The apparatus that may be used for carrying out the invention may comprise conventional NMR imaging apparatus. An example of such apparatus is illustrated in J.Phys.E:Sci.Instrum.. vol 13 (1980) pp 947-955. The apparatus has a resist.We side-access vertical- field magnet operating at 0.04T giving an NMR frequency of 1.7MHz. The apparatus Is modified in that Instead of a single RF transmit/receive coil being used, separate crossed transmit and receive coils are provided. The receive coil Is illustrated in Fig. 1 and comprises a miniature split solenoid 1 of diameter 85mm and length 67mm. Alternatively, coil 1 can be used as a transmit/receive coil with a conventional duplexing arrangement.
An EPR resonator 2 is provided for generating a magnetic field along the axis of the NMR receive coil. EPR resonator 2 is cylindrical and has a diameter of 1Omm and a length of 20mm. A 1% Ic 1 i - 3 sample to be examined is contained i.n a tube 3 positioned within EPR resonator 2. Alternatively, EPR resonator 2 can be aligned at 900 to the receive coil and coaxial with the transmit coil.
EPR resonator 2 Is energised from a separate synthesised microwave frequency generator and the signal is amplified in a broadband amplifier. Resonator 2 itself consists of twenty loops connected in parallel and the parallel connected loops are connected in a parallel resonant circuit. Suitable trimming capacitors are Included to allow resonator 2 to be attuned to the appropriate EPR frequency and matched to cable 4 supplying the EPR excitation. EPR resonator 2 can be replaced by a so-called birdcage resonator, which may be driven in quadrature, as described in J. Mag.Res. 63 pp.222-228(1985). This enables the power applied to the sample by EPR irradiation to be reduced.
The average power applied can be reduced by pulsing the EPR irradiation on and off during the NMR imaging pulse sequence, the EPR irradiation ending immediately before each NMR excitation pulse.
By lowering the static magnetic field strength the enhancement observed from a given sample will be increased for a constant size of EPR resonator and EPR irradiation power. A lower magnetic field strength therefore enables alower concentration of free radicals to be imaged or a larger sample to be examined.
In operation of the apparatus described above a 2.5mM aqueous solution of the nitroxide free radical TEMPOL (4-hydroxy-2,2,6,6 tetramethyl-piperidine-l-oxyl) at room temperature was provided in tube 3, which had an outside diameter of lOmm and a length of 70mm. EPR resonator 2 was Irradiated continuously with mIcrowave power of 1W at a frequency of 1.12GHz and a proton NMR image was obtained by operating the apparatus in accordance with the pulse sequence illustrated in Phys.Med.Biol., vol 25 (1980) pp. 751-756. This sequence Is a saturat i on-re cove ry gradientecho spin-warp pulse sequence. However, other conventional imaging apparatus and other pulse sequences can be used if desired.
i k, Images were acquired on a 128 x 128 matrix, which was Interpolated to 256 x 256 for display, with a field of view of
10cm square. Repetition times varied between 200ms and ls, giving image acquisition times of between 25.6 and 128 seconds.
The experiment was then repeated but with EPR resonator 2 unenergised. The difference between the enhanced and the unenhanced Images was such that an Image enhancement factor of -6.9 was observed. Much larger enhancements can be obtained using free radicals dissolved in organic solvents. Images have also been obtained with TEMPOL concentrations as low as 0.3mM.
The potential of the method described above for oxygen concentration measurement was investigated by imaging simultaneously two identical solutions of 2.5mM TEMPOL solution, one of which had been equilibrated with nitrogen by bubbling the gas through the sample and the other with air. The nitrogen equilibrated sample exhibited a 40% greater enhancement than did the air equilibrated one. This effect occurs because EPR resonances of spin-labels are broadened in the presence of dissolved oxygen. A broad EPR line is more difficult to saturate so that the observed enhancement factor for a given microwave magnetic field stength is reduced.
1.
0
Claims (7)
1. A method of obtaining image Information representing the distribution of paramagnetic molecules in solution comprising the steps of applying radio-frequency radiation to excite EPR resonance in the solute and obtaining an NMR image signal of selected nuclei of the solvent, the signal from those selected nuclei which. interact with electrons excited by the rf radiation being enhanced.
2. The method as claimed in Claim 1 and including the additional steps of obtaining a separate NMR image signal of said selected nuclei which is unenhanced, and deriving image information representing the difference between the enhanced and unenhanced image signals.
3. The method as claimed in either one of the preceding claims in which the said selected nuclei are protons.
4. The method as claimed in any one of the preceding claims in which the said radio-frequency radiation is pulsed.
5. The method as claimed in Claim 4 in which the NMR image signal is obtained by an NMR imaging pulse sequence.
6. The method as claimed in Claim 5 in which the pulses of the 20 said pulsed radio-frequency radiation end before each pulse of the said NMR imaging pulse sequence.
7. A method of obtaining image information representing the distribution of paramagnetic molecules in solution substantially as described herein.
GB Published 1988 at The Patent Office, State House, 66.71 High Halborn, London WC1R 4TP. Further copies may be obtained from The Patent Office, Sales Branch, St Mary Crky. Orpington, Kent BR5 3RD. Printed by Multiplex techniques ltd, St Mary Cray, Kent. Con. 1187.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878718515A GB8718515D0 (en) | 1987-08-05 | 1987-08-05 | Obtaining images |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8818705D0 GB8818705D0 (en) | 1988-09-07 |
| GB2207766A true GB2207766A (en) | 1989-02-08 |
| GB2207766B GB2207766B (en) | 1991-09-04 |
Family
ID=10621841
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB878718515A Pending GB8718515D0 (en) | 1987-08-05 | 1987-08-05 | Obtaining images |
| GB8818705A Expired - Lifetime GB2207766B (en) | 1987-08-05 | 1988-08-05 | Methods of obtaining images representing the distribution of paramagnetic molecules in solution |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB878718515A Pending GB8718515D0 (en) | 1987-08-05 | 1987-08-05 | Obtaining images |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4891593A (en) |
| EP (1) | EP0302742B1 (en) |
| JP (1) | JP2801008B2 (en) |
| DE (1) | DE3854661T2 (en) |
| GB (2) | GB8718515D0 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990013047A1 (en) * | 1989-04-24 | 1990-11-01 | Hafslund Nycomed Innovation Ab | Magnetic resonance imaging method |
| US5314681A (en) * | 1988-12-23 | 1994-05-24 | Nycomed Innovation Ab | Composition of positive and negative contrast agents for electron spin resonance enhanced magnetic resonance imaging |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3865108D1 (en) * | 1987-06-23 | 1991-10-31 | Hafslund Nycomed Innovation | IMAGE GENERATION BY MAGNETIC RESONANCE. |
| GB8819753D0 (en) * | 1988-08-19 | 1988-09-21 | Nycomed As | Apparatus |
| FI80585C (en) * | 1988-11-11 | 1990-07-10 | Instrumentarium Oy | ARRANGEMANG FOER UNDERSOEKNING AV ETT OBJEKT. |
| GB9007636D0 (en) * | 1990-04-04 | 1990-05-30 | Instrumentarium Corp | Mri coil |
| WO1992004640A1 (en) * | 1990-09-06 | 1992-03-19 | British Technology Group Ltd | Method of obtaining images representing the distribution of paramagnetic material in solution |
| GB9024528D0 (en) * | 1990-11-12 | 1991-01-02 | Instrumentarium Corp | Improvements in and relating to magnetic resonance imaging |
| GB9024527D0 (en) * | 1990-11-12 | 1991-01-02 | Instrumentarium Corp | Improvements in and relating to magnetic resonance imaging |
| GB2253702B (en) * | 1991-03-12 | 1995-03-22 | Instrumentarium Corp | apparatus and method |
| GB9216597D0 (en) * | 1992-08-05 | 1992-09-16 | British Tech Group | Method of obtaining images representing the distribution of paramagnetic material in solution |
| US5310851A (en) * | 1993-02-04 | 1994-05-10 | Rohm & Haas | Spin-labelled thickeners |
| DK143193A (en) * | 1993-12-22 | 1995-06-23 | Ardenkjaer Larsen Jan Henrik | Method and apparatus for measuring weak magnetic fields |
| US5528146A (en) * | 1995-01-31 | 1996-06-18 | The University Of Washington | Method and apparatus for detecting electron spin transitions in zero field |
| WO1998054590A1 (en) * | 1997-05-27 | 1998-12-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Resonant structure for spatial and spectral-spatial imaging of free radical spin probes using radiofrequency time domain electron paramagnetic resonance spectroscopy |
| KR100227100B1 (en) * | 1997-09-02 | 1999-10-15 | 한형수 | Water repellent oil repellent, bacteria resistant finishing method of a t/r mix spinning and mixture fabric |
| FI105447B (en) | 1998-11-03 | 2000-08-31 | Raimo Pentti Juhani Joensuu | Arrangement for subject investigation |
| US6673214B1 (en) * | 1999-04-09 | 2004-01-06 | Rocky Mountain Biosystems, Inc. | Energy enhanced reaction catalysis and uses thereof |
| CN101325977A (en) | 2005-12-08 | 2008-12-17 | 皇家飞利浦电子股份有限公司 | System and method for monitoring in vivo drug release using overhauser-enhanced NMR |
| US20230277060A1 (en) * | 2022-03-02 | 2023-09-07 | Mary Hitchcock Memorial Hospital, for itself and on behalf of Dartmouth-Hitchcock Clinic (D/B/A “Dar | Localizing and Imaging Magnetic Nanoparticles Assisted by Electron Paramagnetic Resonance |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4280096A (en) * | 1978-11-07 | 1981-07-21 | Akademie Der Wissenschaften Der Ddr | Spectrometer for measuring spatial distributions of paramagnetic centers in solid bodies |
| US4719425A (en) * | 1986-04-15 | 1988-01-12 | Scientific Innovations, Inc. | NMR imaging method and apparatus |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4238735A (en) * | 1979-02-21 | 1980-12-09 | Varian Associates, Inc. | Indirect detection of nuclear spins of low gyromagentic ratio coupled to spins of high gyromagnetic ratio |
| US4345207A (en) * | 1980-04-24 | 1982-08-17 | The United States Of America As Represented By The Secretary Of The Navy | Method and apparatus for obtaining enhanced NMR signals |
| US4443761A (en) * | 1981-06-16 | 1984-04-17 | National Research Development Corporation | NMR Spectroscopy |
| JPS58142251A (en) * | 1982-02-19 | 1983-08-24 | Jeol Ltd | Nuclear magnetic resonance measurement method |
| US4521732A (en) * | 1982-03-16 | 1985-06-04 | Pegg David T | Pulse sequence for use in performing nuclear magnetic resonance spectroscopy |
| CA1244082A (en) * | 1983-01-10 | 1988-11-01 | Robert T. Gordon | Method for enhancing nmr imaging; and diagnostic use |
| JPS60209155A (en) * | 1984-04-02 | 1985-10-21 | Jeol Ltd | Method for measuring nuclear magnetic resonance |
| US4709212A (en) * | 1986-01-03 | 1987-11-24 | General Electric Company | Method of enhancing image signal-to-noise ratio by combining NMR images of differing pulse sequence timing |
| DE3865108D1 (en) * | 1987-06-23 | 1991-10-31 | Hafslund Nycomed Innovation | IMAGE GENERATION BY MAGNETIC RESONANCE. |
| FI80795C (en) * | 1988-07-01 | 1990-07-10 | Instrumentarium Oy | FARING EQUIPMENT FOR THE PURPOSE OF EXPLOITATION OF AUXILIARY EQUIPMENT. |
-
1987
- 1987-08-05 GB GB878718515A patent/GB8718515D0/en active Pending
-
1988
- 1988-08-01 JP JP63192587A patent/JP2801008B2/en not_active Expired - Fee Related
- 1988-08-04 US US07/228,218 patent/US4891593A/en not_active Expired - Lifetime
- 1988-08-05 DE DE3854661T patent/DE3854661T2/en not_active Expired - Lifetime
- 1988-08-05 EP EP88307252A patent/EP0302742B1/en not_active Expired - Lifetime
- 1988-08-05 GB GB8818705A patent/GB2207766B/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4280096A (en) * | 1978-11-07 | 1981-07-21 | Akademie Der Wissenschaften Der Ddr | Spectrometer for measuring spatial distributions of paramagnetic centers in solid bodies |
| US4719425A (en) * | 1986-04-15 | 1988-01-12 | Scientific Innovations, Inc. | NMR imaging method and apparatus |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5314681A (en) * | 1988-12-23 | 1994-05-24 | Nycomed Innovation Ab | Composition of positive and negative contrast agents for electron spin resonance enhanced magnetic resonance imaging |
| WO1990013047A1 (en) * | 1989-04-24 | 1990-11-01 | Hafslund Nycomed Innovation Ab | Magnetic resonance imaging method |
| AU638985B2 (en) * | 1989-04-24 | 1993-07-15 | Hafslund Nycomed Innovation Ab | Magnetic resonance imaging method |
| US5287854A (en) * | 1989-04-24 | 1994-02-22 | Nycomed Innovation Ab | Electron spin resonance enhanced MRI using an echo planar imaging technique |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2801008B2 (en) | 1998-09-21 |
| DE3854661D1 (en) | 1995-12-14 |
| US4891593A (en) | 1990-01-02 |
| JPS6444837A (en) | 1989-02-17 |
| GB2207766B (en) | 1991-09-04 |
| GB8718515D0 (en) | 1987-09-09 |
| EP0302742A2 (en) | 1989-02-08 |
| GB8818705D0 (en) | 1988-09-07 |
| EP0302742B1 (en) | 1995-11-08 |
| DE3854661T2 (en) | 1996-05-09 |
| EP0302742A3 (en) | 1991-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0302742B1 (en) | Methods of obtaining images representing the distribution of paramagnetic molecules in solution | |
| US5735795A (en) | Marker for magnetic resonance imaging | |
| US10627463B2 (en) | Simultaneous TX-RX for antenna devices | |
| US4719425A (en) | NMR imaging method and apparatus | |
| US9625551B2 (en) | Magnetic resonance apparatus and data acquisition method with decoupling between transmit and receive coils | |
| US4728896A (en) | Method and apparatus for obtaining N.M.R. spectra and coils for use therein | |
| JPH0350537B2 (en) | ||
| JP2003180655A (en) | Method for measuring location of object in mr system, and catheter and mr system for performing the method | |
| US4906931A (en) | Apparatus and method for the examination of properties of an object | |
| US6573720B1 (en) | Resonant structure for spatial and spectral-spatial imaging of free radical spin probes using radiofrequency time domain electron paramagnetic resonance spectroscopy | |
| CN105259524B (en) | Dynamic Field Acquisition in Magnetic Resonance Tomography | |
| US4684892A (en) | Nuclear magnetic resonance apparatus | |
| EP0654146B1 (en) | Method of obtaining images representing the distribution of paramagnetic material in solution | |
| Nicholson et al. | Recent developments in combining LODESR imaging with proton NMR imaging | |
| JPH0924037A (en) | Magnetic resonance device and method | |
| US9069048B2 (en) | Broadband decoupling pulse trains with interleaved pauses for magnetic resonance spectroscopy | |
| EP0797102B1 (en) | A device for excitation and detection of magnetic resonance | |
| US6466812B1 (en) | MR method for generating enhanced nuclear magnetization | |
| EP4246166A1 (en) | Improved low field magnetic resonance imaging instrumental system and methods of use | |
| US4816764A (en) | Method for the identification of nuclear magnetic spectra from spatially selectable regions of an examination subject | |
| Placidi et al. | Two-dimensional 220 MHz Fourier transform EPR imaging | |
| US5467016A (en) | Saturation selective spectroscopic imaging | |
| Capozzi et al. | A low frequency 1H-NMR external unit for the analysis of large foodstuff samples | |
| WO1992004640A1 (en) | Method of obtaining images representing the distribution of paramagnetic material in solution | |
| JPH0694820A (en) | Pulse adjusting method of nuclear magnetism resonator device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
| PE20 | Patent expired after termination of 20 years |
Expiry date: 20080804 |